RNAi epimutations conferring antifungal drug resistance are inheritable

Carlos Pérez-Arques (), María Isabel Navarro-Mendoza (), Ziyan Xu, Grit Walther and Joseph Heitman ()
Additional contact information
Carlos Pérez-Arques: Duke University School of Medicine
María Isabel Navarro-Mendoza: Duke University School of Medicine
Ziyan Xu: Duke University School of Medicine
Grit Walther: Hans Knöll Institute
Joseph Heitman: Duke University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract Epimutations modify gene expression and lead to phenotypic variation while the encoding DNA sequence remains unchanged. Epimutations mediated by RNA interference (RNAi) and/or chromatin modifications can confer antifungal drug resistance and may impact virulence traits in fungi. However, whether these epigenetic modifications can be transmitted across generations following sexual reproduction was unclear. This study demonstrates that RNAi epimutations conferring antifungal drug resistance are transgenerationally inherited in the human fungal pathogen Mucor circinelloides. Our research reveals that RNAi-based antifungal resistance follows a DNA sequence-independent, non-Mendelian inheritance pattern. Small RNAs (sRNAs) are the exclusive determinants of inheritance, transmitting drug resistance independently of other known repressive epigenetic modifications. Unique sRNA signature patterns can be traced through inheritance from parent to progeny, further supporting RNA as an alternative molecule for transmitting information across generations. Understanding how epimutations occur, propagate, and confer resistance may enable their detection in other eukaryotic pathogens, provide solutions for challenges posed by rising antimicrobial drug resistance, and advance research on phenotypic adaptability and its evolutionary implications.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62572-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62572-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62572-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().